依达拉奉-β-环糊精包合物的分子模拟研究

Molecular simulation investigation ofβ-cyclodextrin inclusion of edaravone

环糊精主客体包合物在药剂学方面具有众多的应用,药物分子形成环糊精包合物后具有缓释、控释、提高疗效和降低毒副作用等功能。为了消除普通依达拉奉药物的不良反应,本文用分子动力学模拟和量子化学计算2种方法模拟了依达拉奉的β-环糊精包合物的动态稳定性,并分析了该包合物的相对稳定结构。通过对分子模拟结果的分析,揭示了依达拉奉的2种β-环糊精包合物的相对稳定性,得出了依达拉奉的β-环糊精包合物的最稳定结构为:依达拉奉分子的杂环位于β-环糊精的窄口处。根据量子化学计算对单体和包合物的化学热力学分析,进一步得出了包合物的稳定能和优势稳定结构,并对分子动力学模拟的结果进行了验证。

The host-guest inclusion complex of cyclodextrin has numerous applications in pharmacy, drug molecules in their cyclodextrin inclusion complex have many unique functions, such as slow-release, controlled release, improve efficacy and reduced toxicity. In order to eliminate the adverse side effect of the common edaravone, the dynamics structures and trajectories in vacuum of two β-cyclodextrin inclusions of edaravone have been simulated by using molecular dynamics simulation. By means of the molecular simulation, we investigated the inclusion structure of the host-guest complex and its physicochemical stability, and drown a conclusion that the A-type β-cyclodextrin inclusion complex of edaravone has a more reasonable inclusion structure than B-type, because A-type β-cyclodextrin inclusion of edaravone not only has stronger intermolecular H-bonding interaction and intermolecular hydrophobic interaction than B-type inclusion, but also has a more perfect inclusion structure than B-type inclusion. Finally, thermodynamic energies of the host, guest and their inclusion complexes as well as their inclusion stability energy calculated by means of the quantum chemistry calculation also prove that A-type β-cyclodextrin inclusion of edaravone is more stable than B-type inclusion on thermodynamics. Therefore, the A-type β-cyclodextrin inclusion of edaravone is the favorable β-cyclodextrin inclusion. And the validity of the molecular dynamics simulation and quantum chemistry calculation was well proved by each other. Those results provide a theoretical guidance for the development of new drugs.